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Synthesis 2006(9): 1437-1442  
DOI: 10.1055/s-2006-926433
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 4,4′-Disubstituted Azepines via Ring-Closing Metathesis Reaction and Asymmetric Arylation of Lactones

Laurent Delhaye, Alain Merschaert*, Khalid Diker, Ioannis N. Houpis*
Chemical Product Research and Development, Lilly Development Centre, rue Granbonpré 11, 1348 Mont-St-Guibert, Belgium
Fax: +32(10)476315; e-Mail: merschaert_alain@lilly.com; e-Mail: yhoupis@prdbe.jnj.com ;
Further Information

Publication History

Received 8 December 2005
Publication Date:
11 April 2006 (online)

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Abstract

The syntheses of the title compounds were accomplished via an original sequence of reactions including the ring-closing metathesis­ of ω-dienes by using the second-generation Grubbs’ catalyst. The chiral diene precursors are available in racemic or optically enriched form from the corresponding α,α′-disubstituted lactones derivatives

Key words

heterocycles - ring closure - metathesis - butyrolactone - arylation

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1

Current address: J&J PRD, Turnhoutseweg 30, 2340 Beerse, Belgium.

2

A search in the mddr-3d Isis database produced >1000 hits of azepine derivatives in various stages of development.

6

With the exception of compounds 9 (unstable), all isolated compounds in this work gave satisfactory 1H and 13C NMR spectra and HRMS or favorable comparison with the literature data.

11

Compounds 4a and 4b and their subsequent derivatives are volatile and were not isolated. Overall yields are reported for 9a and 9b.

16

Tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene][benzylidine]ruthenium (IV) dichloride: CAS number [246047-72-3].